Thomas T. Tidwell

FRET Quenching of Photosensitizer Singlet Oxygen Generation

The development of activatable photodynamic therapy (PDT) has demonstrated a utility for effective photosensitizer quenchers. However, little is known quantitatively about Forster resonance energy transfer (FRET) quenching of photosensitizers, even though these quenchers are versatile and readily available. To characterize FRET deactivation of singlet oxygen generation, we attached various quenchers to the photosensitizer pyropheophorbide-alpha (Pyro) using a lysine linker. The linker did not induce major changes in the properties of the photosensitizer. Absorbance and emission wavelength maxima of the quenched constructs remained constant, suggesting that quenching by ground-state complex formation was minimal. All quenchers sharing moderate spectral overlap with the fluorescence emission of Pyro (J > or = 5.1 x 10(13) M(-1) cm(-1) nm4) quenched over 90% of the singlet oxygen, and quenchers with weaker spectral overlap displayed minimal quenching. A self-quenched double Pyro construct exhibited intermediate quenching. Consistent with a FRET deactivation mechanism, extension of the linker to a 10 residue polyproline peptide resulted in only the quenchers with spectral overlap almost 2 orders of magnitude higher (J > or = 3.7 x 10(15) M(-1) cm(-1) nm4) maintaining high quenching efficiency. Overall, there was good correlation (0.98) between fluorescence quenching and singlet oxygen quenching, implying that fluorescence intensity can be a convenient indicator for the singlet oxygen production status of activatable photosensitizers. Uniform singlet oxygen luminescence lifetimes of the compounds, along with minimal triplet state transient absorption were consistent with quenchers primarily deactivating the photosensitizer excited singlet state. In vitro, cells treated with well-quenched constructs demonstrated greatly reduced PDT induced toxicity, indicating that FRET-based quenchers can provide a level of quenching useful for future biological applications. The presented findings show that FRET-based quenchers can potently decrease singlet oxygen production and therefore be used to facilitate the rational design of activatable photosensitizers.

Hydrodeoxygenation of hydroxy, methoxy and methyl phenols with molybdenum oxide/nickel oxide/alumina catalyst

Hydrodeoxygenation (HDO) with MoO3-NiO-Al2O3 catalyst gives markedly different results for the isomeric dihydroxybenzenes, in contrast to previous studies with molybdenum or other catalysts which suggested similar behavior for these substrates. Thus, at 350°C o-dihydroxybenzene is more reactive than phenol and gives 60% of phenol, m-dihydroxybenzene is much less reactive and gives primarily ring saturation and p-dihydroxybenzene is more reactive than phenol and gives primarily products of ring saturation. At 500 °C total conversion of all three isomers is achieved. Other substrates studied are o-methoxyphenol, 2, 6-dimethoxyphenol and various methyl- and dimethylphenols. Reaction variables examined include temperature, the effects of added H2O and MeOH and repeated use of the same catalyst batch for successive runs. The results are interpreted in terms of the geometries of the substrates and their ability to adsorb on the catalyst surface, the blocking of active sites on the catalyst by H2O and MeOH either generated during HDO or added directly and the different electronic properties of the substrates.

Wilhelm Schlenk: The Man Behind the Flask

In 1943 there appeared in Berichte der Deutschen Chemischen Gesellschaft[1] a brief notice (Figure 1) of the death of Wilhelm Schlenk, the former President of the German Chemical Society (Deutsche Chemische Gesellschaft).[2a] It was stated that a fuller biography of Schlenk would appear later, but this has not been forthcoming, although there were short articles in specialized Austrian[2b] and Bavarian[2c] journals. Underneath the notice about Schlenk there was a list of individuals who had died in 1942, and this list was headed by the traditional German Iron Cross, emblazoned with the swastika, the emblem of the ruling National Socialist Party led by Adolf Hitler. A name that stands out on this list is that of Max Bodenstein, another pioneer in free radical chemistry and one of Schlenk s successors as President of the Deutsche Chemische Gesellschaft (1930 ± 1932), for whom a detailed memorial appeared in 1967.[2d] The name Schlenk is familiar to many chemists because of the widespread use of aSchlenko glassware, as illustrated in many textbooks and reviews on the handling of air-sensitive compounds.[3] Who was Schlenk, and why has the promised obituary never appeared? A brief study of the life of this extraordinary scientist provides an answer to the first question, and also makes a strong case that he should be better known, not only for his scientific achievements but also for the example he set as a man of principle and political courage. Wilhelm Johann Schlenk (Figure 2) was born in Munich in 1879, the son of Georg and Emilie Schlenk, and attended the Realgymnasium there. He had a fine singing voice and considered a career in music, but instead followed the example of his brother Johann Oskar Schlenk (1874 ± 1951; Figure 2, right) in the study of chemistry. Another brother Hermann became a Director of the Löwenbräu brewery in

Solvolytic reactivity of 1-trifluoromethyl-1-phenylethyl tosylate. Correlation of substituent effects in the formation of highly destabilized carbonium ions

The solvolytic rate constants of 1-trifluoromethyl-1-phenylethyl toxylate (2) in solvents of widely different ionizing power and nucleophilicity are linearly related with slope mlt. slashsub OTslt. slash = 1.01 to the rates of 2-adamantyl tosylate in the same solvents. The rate ratio k(PhCHMeOTs)/k(2) is 2 x 10/sup 5/ in 100% EtOH. Added salts cause modest increases in the rate of solvolysis of 2 in 80% EtOH independent of the nucleophilicity or basicity of the salts. The isotope effect k(CH/sub 3/)/k(CD/sub 3/) on the rate of solvolysis of 2 ranges from values around 1.6 in the less ionizing solvents to values around 1.3 in more ionizing solvents. The product from 2 is mainly that of substitution in all solvents studied, with increasing amounts of elimination in the less ionizing solvents. These results are interpreted in terms of rate-limiting ionization of 2 to form a carbonium ion intermediate.

The Gomberg century: Free radicals 1900–2000

Abstract In summary, the science of free radical chemistry showed remarkable advancement during the Century following Gombergs seminal contribution in 1900. The current vigor of the field shows that the impetus provided by the pioneers mentioned in this brief survey is by no means spent. The breadth of the field indicates that any future comprehensive survey will be a major undertaking. However, there are recent concise descriptions of the field that are highly recommended. 398, 399

N-pyrrolylketene: a nonconjugated heteroarylketene.

N-Pyrrolylketene (5) is calculated to be destabilized and nonconjugated, with a preferred geometry with the pyrrolyl ring orthogonal to the ketenyl group. Ketene 5 is generated from N-pyrrolylacetic acid (7) with use of Mukaiyamas reagent, and reacts with imines forming β-lactams 10, with a product ratio correlation of log(cis/trans) with σ(+). Photolysis of N-diazoacetylpyrrole (14) in MeOH gives methyl N-pyrrolylacetate (15) from 5 and also ester 17, evidently by trapping of 2-(1-pyrrolylketene) (21), formed by a new vinylogous Wolff rearrangement.

Isomerization of Triphenylmethoxyl: The Wieland Free‐Radical Rearrangement Revisited a Century Later

yielded 2.3 g of a yellow oil from which benzophenone (almost 2 g) and phenol (0.2 g) were separated. Further heating gave a substantial, but not quantifiable, amount of Ph3COH. Wieland s interpretation was that triphenylmethoxyl radicals (Ph3COC, 2) had been formed and had isomerized to Ph2(PhO)CC radicals (3) which then coupled (Scheme 1). This was the first clearly demonstrated, and explicitly shown, free-radical rearrangement—a priority often overlooked. The rate constants and mechanisms of isomerization of triphenylmethoxyl (2) and the analogous isomerizations of Ph2C(Me)OC (5), [2–10] and related radicals (Scheme 2), have received considerable attention. Claims that discrete spiro intermediates (6) had been identified in the rearrangements of 2 and 5 3] have been disproven. However, computational studies on the rearrangement of 5 10] (and PhCH2OC) [11] do indicate stepwise processes with spiro radicals (6) as intermediates (Scheme 2). Consistent with these calculations, cumyloxyl radicals, PhC(Me)2OC, para substituted with a 2,2-diphenylcyclopropyl reporter group, have been demonstrated to be in equilibrium with spiro radicals 6. Rate constants (10 6 k2 s ) measured at room temperature by laser flash photolysis (LFP) in CH3CN were 2.5, [6]

Heptafulvenone, Vinylketene, Butadienylketene, and Allenylketene − Facile Generation, Observation, and Radical Reaction with TEMPO

Heptafulvenone (1), vinylketene (11), 1,3-butadienylketene [(E)-15], and allenylketene (21) have been prepared by reaction of the corresponding acyl chlorides with 1,8-bis(dimethylamino)naphthalene as long-lived species in solution at room temperature, and their ketenyl IR bands observed under these conditions for the first time, at 2101, 2118, 2111, 2117 cm−1, respectively. These unsaturated ketenes react with tetramethylpiperidinyloxyl (TEMPO, TO·) with initial attack at the carbonyl carbon giving delocalized radicals which give from 1 a mixture of the ring contracted o-, m-, and p-formylbenzoates O=CHC6H4CO2T (6) and the bis(cycloheptatrienyl) dimer 7. The products from 11, (E)-15, and 21 are the bis(TEMPO) adducts (E,Z)-TOCH2CH=CHCO2T (12), (E,E)-TOCH2CH=CHCH=CHCO2T (17), and (E,Z)-CH2=C(OT)CH=CHCO2T (22), respectively.

TRIMETHYLSILYLKETENE : REACTIVITY AND STABILIZATION

Abstract Me 3 SiCHCO is stable thermally, and is less reactive than t BuCHCO toward H 2 O in neutral hydration, but in acid and base induced hydrations the reactivity is accelerated relative to alkylketenes. The contrasting reactivities are due to the relative degree of silicon stabilization of the ground state and the different transition states.

Spiro-Aziridine and Bislactam Formation from Bisketene−Imine Cycloadditions

1,2-Bisketenes 6 react with imines PhCHNAr, (E)-2, forming spiro-aziridines 7. DFT computations indicate that this occurs by nucleophilic attack of the imine on the carbonyl carbon of the more reactive arylketene moiety, followed by cyclization, and not by prior cyclization of the 1,2-bisketene forming a carbene lactone intermediate. Computations also indicate that the previously studied bisketene 10 from benzocyclobutadiene 9 is 4.0 kcal/mol less stable than carbene lactone 12 that would result from cyclization but that the failure to observe 12 results from a lower barrier for 10 to instead revert to 9. 1,2-, 1,3-, and 1,4-Bisketenylbenzenes 16, 19, and 22 react with imines forming bis(β-lactams), with a preference for formation of mixtures of trans, trans chiral (±) and achiral diastereomeric products.